JP2005007225A

JP2005007225A - Sample mixing method and device therefor

Info

Publication number: JP2005007225A
Application number: JP2003171529A
Authority: JP
Inventors: Kazunori Hake; 一徳吐合
Original assignee: Yaskawa Electric Corp
Current assignee: Yaskawa Electric Corp
Priority date: 2003-06-17
Filing date: 2003-06-17
Publication date: 2005-01-13
Anticipated expiration: 2023-06-17
Also published as: JP4349005B2

Abstract

<P>PROBLEM TO BE SOLVED: To provide a sample mixing device which efficiently mixes and stirs a plurality of samples. <P>SOLUTION: The sample mixing device is provided with a flow channel 7 consisting of substrates 10 and 11, a magnetic field generation part 12 which is provided adjacently to the flow channel and generates a magnetic field in the direction vertical to the direction of the flow of the samples and a controller 6 which controls the magnetic field of the magnetic field generation part. The sample mixing device magnetically mixes and stirs a composite sample, in which the different kinds of the samples are roughly mixed, by generating a magnetic field in the direction vertical to the direction of the flow of the composite sample by the magnetic field generation part. The magnetic field generation part can be a magnetic field generation pair 15 which are arranged oppositely to each other across the flow channel. The magnetic field generation part can be provided with a cylindrical stirring part formed by making the area of a part of the flow channel large, a flowing-in port 4 provided at the center part of the stirring part and a flowing-out port 5 provided on the surface of the wall of the stirring part, and the magnetic field generation pair can concentrically be arranged in the direction of the flow of the composite sample. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は、創薬、有機合成、化学分析等で利用されるマイクロ流路における複数の分子や試料等を混合攪拌する試料混合方法及び装置に関する。
【０００２】
【従来の技術】
従来の試料混合方法及び装置は、マイクロ流路内に攪拌部を設け、前記混合部に配置した光圧ミキサにより液中で直接、混合攪拌を行っている（例えば、特許文献１参照）。
【０００３】
【特許文献１】特開２００１−２５２８９７号公報（第２図）
【０００４】
図８は、従来の試料混合装置を示す断面図である。図において２は混合試料、４は流入口、５は流出口、７は流路、５０は光圧ミキサ、５１は攪拌槽、５２は試料ａ、５３は試料ｂであり、流入口４より試料ａ５２と試料ｂ５３を流入させて攪拌槽５１に導入し、前記攪拌槽に配設された光照射により生ずる光圧を駆動力として回転する光圧ミキサ５０にレーザ光等を照射することで前記攪拌槽において回転させ、前記攪拌槽で前記試料ａ及び試料ｂに対流を誘起して２液を能動的かつ直接的に混合攪拌する。
このように、従来の試料混合方法及び装置は、攪拌槽に光圧ミキサを配置することで機械的な駆動源を有することなく光照射により容易に混合攪拌を行うのである。また、前記攪拌槽で発生する対流を直接的に混合攪拌に利用することで混合試料の混合効率を飛躍的に増大させ、反応速度を向上させるのである。
【０００５】
【発明が解決しようとする課題】
しかしながら、従来の試料混合方法及び装置は、流路内に直接、光圧ミキサを配設する必要があるため、マイクロ流路を含めた製作工程が複雑となり、流路幅が狭くなるに従って加工が難しくなるという問題があった。また、光圧ミキサの駆動源として光源を利用するため、光透過性の悪い材質を基板として用いることができず、混合攪拌できる試料も光透過度により混合効率の低下を招く恐れがあるという問題があった。さらに、機械的に対流を発生させて混合攪拌を行うため、光圧ミキサの回転時に試料に損傷を与える恐れがあるというような問題も抱えていた。
そこで、本発明はこのような問題点に鑑みてなされたものであり、流路内に直接、混合攪拌するための手段を講じることなく複数の試料を効率よく混合攪拌できる試料混合方法及び装置を提供することを目的とする。
【０００６】
【課題を解決するための手段】
上記問題を解決するため、本発明は、次のように構成したものである。
請求項１に記載の発明は、異なる種類の試料が粗混合された複合試料を、流路にて混合攪拌する試料混合方法において、前記流路の近傍に磁界を発生する磁界発生部を設け、この磁界発生部により前記複合試料の流れ方向に対して垂直方向の磁界を形成し、前記複合試料を磁気的に混合攪拌するものである。
このようになっているため、試料の流れ方向と垂直方向に磁気流を発生でき、試料を二次元的に混合攪拌を行うことができる。また、試料に対して物理的な力を加えることが無いため、試料の損傷を抑制することができると共に、試料と非接触に混合攪拌を行うことができ、接液による不純物の混入を抑えることができる。
請求項２に記載の発明は、前記磁界を周期的に強度が変わる振動磁界としたものである。
このようになっているため、磁界により流路内に形成した磁気流を試料の流れ方向に対して垂直方向に交互に発生させることができ、連続的な混合攪拌と攪拌性能を向上することができる。また、小刻みな振動磁界を発生させることで試料の損傷を抑えることができる。
請求項３に記載の発明は、前記磁界を周期的に強度が変わる振動磁界としたものである。
このようになっているため、熱エネルギーの損失を抑えることができ、攪拌効率を向上することができる。また、磁気流を微動化させることができ、試料の損傷を抑えることができる。
請求項４に記載の発明は、前記磁界を前記流路を挟んで対向配置した磁界発生対により形成したものである。
このようになっているため、流路内部にかける磁場を容易に大きくすることができ、高い粘度や低い移動度の試料も効率よく混合攪拌することができる。
請求項５に記載の発明は、前記流路の一部を円筒形状の撹拌部とし、前記試料を前記撹拌部の中心部から前記流路の流れ方向と直角方向に流入させて前記撹拌部の壁面より流出させ、かつ前記磁界を前記試料の流れ方向に同心円状に形成し、順次磁界を発生させて回転磁場を形成したものである。
このようになっているため、試料の流れ方向とは別に流路内で円状の流れ（渦流）を形成することができ、攪拌性能を向上することができる。また、円中心部から放射状に試料を供給することで全ての試料を確実に混合攪拌することができる。
請求項６に記載の発明は、前記回転磁場は、半径方向に磁場の方向が交互に変わるようにしたものである。
このようになっているため、回転磁場間で磁気流の摩擦が生じ、試料の衝突頻度を向上することができる。
請求項７に記載の発明は、前記試料は、磁化特性を有する成分を含ませたものである。
このようになっているため、磁場形成による磁気力によって直接、試料を混合攪拌することができる。また、試料自身が磁化特性を有しなくとも試料中に磁化特性を有する成分が含まれていることで前記成分の攪拌により目的とする試料を間接的に混合攪拌することが可能となり、攪拌性能を向上することができる。
請求項８に記載の発明は、基板からなる流路と、前記流路近傍に設けられ前記試料の流れ方向に対して垂直方向に磁界を発生させる磁界発生部と、前記磁界発生部の磁界を制御するコントローラとを備えたものである。
このようになっているため、試料の流れ方向と垂直方向に磁気流を発生でき、試料を二次元的に混合攪拌を行うことができる。また、試料に対して物理的な力を加えることが無いため、試料の損傷を抑制することができると共に、試料と非接触に混合攪拌を行うことができ、接液による不純物の混入を抑えることができる。
請求項９に記載の発明は、前記磁界発生部は、前記流路を挟んで対向配置した磁界発生対としたものである。
このようになっているため、流路内部にかける磁場を容易に大きくすることができ、高い粘度や低い移動度の試料も効率よく混合攪拌を行うことができる。
請求項１０に記載の発明は、前記磁界発生対は、前記磁界発生部の少なくとも一方に磁性材料を設けたものである。
このようになっているため、磁界方向を一方の磁界発生部のみで調整でき、構造を簡素化することができる。
請求項１１に記載の発明は、前記流路の一部を円筒形状とした混合部と、前記混合部の中心部に設けた流入口と、前記撹拌部の壁面に設けた流出口とを備え、前記磁界発生対を前記試料の流れ方向に同心円状に配置したものである。
このようになっているため、磁界発生部の配置順に従って順次磁界を発生させ、試料の流れ方向とは別に流路内で円状の流れ（回転磁界）を形成することができ、攪拌性能を向上することができる。また、円中心部から放射状に試料を供給することで全ての試料を確実に混合攪拌することができると共に、隣接する回転磁場方向が逆方向になるように磁界を発生させることで、回転磁場間で磁気流の摩擦により試料の衝突頻度を向上することができる。
請求項１２に記載の発明は、前記磁界発生部を前記流路を形成する基板と独立して配置したものである。
このようになっているため、磁界発生部の異常や流路の目詰り等による不具合時に必要な部分のみを容易に交換でき、保守性能を向上することができる。また、磁界発生部と接液する部分が分離でき、磁界発生部を再利用することができると共に、不純物の混入を抑制することができる。
【０００７】
【発明の実施の形態】
以下、本発明の具体的実施例を図に基づいて説明する。
【０００８】
（第１実施例）
図１は、本発明の第１実施例を示す試料混合装置の断面図である。図において、共通する部分には同一符号を用いてあり、１は複合試料、２は混合試料、３は送液装置、４は流入口、５は流出口、６はコントローラ、７は流路、１０は上基板、１１は下基板、１２は磁界発生部、１４は磁界方向となっている。
複合試料１としては蛍光色素と酵母菌より抽出したＤＮＡ断片を用い、シリンジ駆動の送液装置３よりマイクロ流路の流入口４に導入した。流路７は断面が５００μｍ×２００μｍ、長さ５０ｍｍのものを用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
マイクロ加工された流路７の流入口４より送液装置３を用いて複合試料１を規定流量で導入する。次に、上基板１０に配置された磁界発生部１２にコントローラ６より信号を入力することにより流路７を介して上基板１０と下基板１１間に磁束が発生する。前記磁束は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。次に逆向きの磁束を発生させると複合試料１は先程とは逆方向の磁気流によって、再度、混合攪拌が行われる。磁界方向１４に示すように磁界の往復動作を連続的に行うことで混合試料２を効率的に採取することができる。
例えば、合計１０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【０００９】
（第２実施例）
図２は、本発明の第２実施例を示す試料混合装置の断面図である。図において、１５は磁界発生対である。
第１実施例と同様な複合試料１及び流路７を用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
マイクロ加工された流路７の流入口４より送液装置３を用いて複合試料１を規定流量で導入する。次に、上基板１０および下基板１１に配置された磁界発生部１２にコントローラ６より信号を入力することにより流路７を介して上基板１０と下基板１１間に磁束が発生する。例えば、磁界方向１４が下向きの場合は、上基板１０に配置した磁界発生部１２を流路７内に向けた方向に、下基板１１に配置した磁界発生部１２を流路７から下基板１１外に向けた方向にそれぞれ磁束を形成させる。前記磁束は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。磁界方向１４が上向きの場合はそれぞれの基板にかける磁束を逆方向にすることで複合試料１は先程とは逆方向の磁気流を発生させ、再度、混合攪拌が行われる。磁界方向１４に示すように磁界発生対１５間で磁界の往復動作を連続的に行うことで混合試料２を効率的に採取することができる。基本的にコントローラ６から磁界発生対１５に印加する信号を上基板１０と下基板１１間で同期させることで単独の磁界発生部１２の磁束に比べて高い合成磁束を得ることができ、効率的な混合攪拌を促進させることができる。
例えば、合計１０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【００１０】
（第３実施例）
図３は、本発明の第３実施例を示す試料混合装置の横断面図、図４は図３の上断面図である。図において、２０は回転磁場ａ、２１は回転磁場ｂ、２２は回転磁場ｃである。
第１実施例と同様な複合試料１を用い、及び流路７は直径４０ｍｍで高さが２００μｍのものを用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
円盤状にマイクロ加工された流路７の円中心部に流入口４を設け、送液装置３により複合試料１を規定流量で流路７内に導入すると、複合試料１は流入口４から放射状にほぼ均等に流路７内を流れる。ここで、上基板１０に配置された磁界発生部１２にコントローラ６より信号を入力することにより流路７を介して上基板１０と下基板１１間に磁束を発生させる。前記磁界は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。次に、上基板１０にかける磁束を逆方向にすることで複合試料１は先程とは逆方向の磁気流の発生によって、再度、混合攪拌が行われる。
また、図４のように同心円状に磁界発生部１２を構成することで回転磁場を形成し、磁気流を渦巻き状にすることで複合試料１を動かすことができる。例えば、回転磁場ａ２０をａ、ｂ、ｃ・・・ｈ、ａと時計回りに磁場を形成すると、流路７内は正弦波的な磁気流を得ることができ、複合試料１は時計回りの力を受ける。従って、複合試料１は放射状に進む力と、流れ方向に対して垂直な向きの力と、時計回りの力を受けることとなり、３次元的な混合攪拌が行われ、混合率を大幅に高めることができる。回転磁場ｂ２１と回転磁場ｃ２２を含めて全て右回りにすると大きな渦流をえることができる。また、回転磁界ａ２０を時計回り、回転磁界ｂ２１を反時計回り、回転磁界ｃ２２を時計回りに形成すると、各回転磁界の境界部で大きな摩擦が発生し、より高い混合率を得ることができる。混合試料２は複数個設けられた流出口５より順次、排出される。
例えば、合計２０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【００１１】
（第４実施例）
図５は、本発明の第４実施例を示す試料混合装置の断面図である。図において、１３は磁性材料である。
第１実施例と同様な複合試料１を用い、流路７は第３実施例と同様なものを用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
円盤状にマイクロ加工された流路７の円中心部に流入口４を設け、送液装置３により複合試料１を規定流量で流路７内に導入すると、複合試料１は流入口４から放射状にほぼ均等に流路７内を流れる。ここで、上基板１０に配置された磁界発生部１２にコントローラ６より信号を入力することにより流路７を介して上基板１０と下基板１１間に磁束を発生させる。このとき、下基板１１には磁界発生対１５を成す磁性材料１３が配置されており、上基板１０に配置された磁界発生部１２の強さに応じて流路７内の磁界方向１４を変化させる。磁界方向１４は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。次に、上基板１０にかける磁束を逆方向にすることで複合試料１は先程とは逆方向の磁気流の発生によって、再度、混合攪拌が行われる。磁界発生部１２の替わりに磁性材料１３を用いることで装置の簡素化、小型化を達成できると共に、コントローラ６にも複雑な要素を必要としない。
例えば、合計２０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【００１２】
（第５実施例）
図６は、本発明の第５実施例を示す試料混合装置の断面図である。
第１実施例と同様な複合試料１を用い、流路７は第３実施例と同様なものを用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
円盤状にマイクロ加工された流路７の円中心部に流入口４を設け、送液装置３により複合試料１を規定流量で流路７内に導入すると、複合試料１は流入口４から放射状にほぼ均等に流路７内を流れる。ここで、上基板１０とした基板１１に配置された磁界発生部１２にコントローラ６より信号を入力することにより流路７を介して上基板１０と下基板１１間に磁束を発生させる。磁界方向１４は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。次に、上基板１０にかける磁界を逆方向にすることで複合試料１は先程とは逆方向の磁気流によって、再度、混合攪拌が行われる。
上基板１０と下基板１１には磁界発生対１５を成す磁界発生部１２が各々配置されており、各磁界発生対１５における合成磁界に応じて流路７内の磁界方向１４を変化させる。また、実施例３と同様に同心円状に磁界発生部１２を構成することで回転磁場を形成し、複合試料１を渦巻き状の磁気流によって動かすことができるため、複合試料１は放射状に進む力と、流れ方向に対して垂直な向きの力と、時計回りの力を受けることとなり、３次元的な混合攪拌が行われ、混合率を大幅に高めることができる。また、隣接する回転磁界を逆向きで構成することで各回転磁界の境界部で大きな摩擦が発生し、より高い混合率を得ることができる。基本的にコントローラ６から電極対１５に印加する信号を上基板１０と下基板１１間で同期させることで単独の磁界発生部１２の磁束に比べて高い合成磁束を得ることができ、効率的な混合攪拌を促進させることができる。
例えば、合計２０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【００１３】
（第６実施例）
図７は、本発明の第６実施例を示す試料混合装置の断面図である。図において、１６は磁極上基板、１７は磁極下基板である。
第１実施例と同様な複合試料１を用い、流路７は第３実施例と同様なものを用い、磁界発生部１２にはマイクロ加工された電磁石を用いた。
次に、本実施例の動作について説明する。
円盤状にマイクロ加工された流路７の円中心部に流入口４を設け、送液装置３により複合試料１を規定流量で流路７内に導入すると、複合試料１は流入口４から放射状にほぼ均等に流路７内を流れる。磁界発生部１２を配置した磁極上基板１６と磁極下基板１７を上基板１０と下基板１１にそれぞれ配置し、磁界発生部１２にコントローラ６より信号を入力することで流路７を介して上基板１０と下基板１１間に磁束を発生させる。磁界方向１４は複合試料１の流れ方向に対して垂直方向に形成されるため、複合試料１内に前記磁束による磁界が形成されることによって複合試料１が力を受けて磁気流が発生し、前記磁気流により複合試料１が平均自由工程に起因する衝突反応を引き起こし、流路７内で混合攪拌される。次に、上基板１０にかける磁束を逆方向にすることで複合試料１は先程とは逆方向の磁気流によって、再度、混合攪拌が行われる。
各磁界発生対１５における合成磁界に応じて流路７内の磁界方向１４を変化させ、実施例３と同様に同心円状に磁界発生部１２を構成することで回転磁場を形成し、複合試料１を渦巻き状に動かすことができるため、複合試料１は放射状に進む力と、流れ方向に対して垂直な向きの力と、時計回りの力を受けることとなり、３次元的な混合攪拌が行われ、混合率を大幅に高めることができる。また、隣接する回転磁界を逆向きで構成することで各回転磁界の境界部で大きな摩擦が発生し、より高い混合率を得ることができる。基本的にコントローラ６から電極対１５に印加する信号を上基板１０と下基板１１間で同期させることで単独の磁界発生部１２の磁束に比べて高い合成磁束を得ることができ、効率的な混合攪拌を促進させることができる。磁界発生部１２を各基板内に埋め込みとしていないため、磁界発生部の異常や流路の目詰り等による不具合時に必要な部分のみを容易に交換でき、保守性能を向上することができる。また、磁界発生部１２と接液する部分が分離できるため、不純物の混入を抑制することができる。磁界発生部１２自身をリニア構造とすることでより微細な加工を施すことができる。
例えば、合計２０μＬ／ｍｉｎで供給した複合試料１を混合攪拌して混合試料２を採取し、蛍光分析装置で混合率を発光強度で測定したところ、混合率の改善を確認することができた。
【００１４】
なお、本実施例では複合試料１として蛍光色素と酵母菌より抽出したＤＮＡ断片を用いたが、試料自身の末端に磁化特性を有する成分を予め結合させたものを用いることで、磁束形成による磁場によって直接、試料を混合攪拌することができる。また、試料自身が磁化特性を有しなくともバッファー液中に磁化特性を有する成分が含まれていることで前記成分の攪拌により目的とする試料を間接的に混合攪拌することが可能となり、攪拌性能を向上することができる。
各試料の搬送装置３としてポンプを用いたが、電気泳動的な搬送手段を用いても同様の効果が得られる。磁界発生部１２は実施例に示される形状のみではなく、特に各磁界発生対における合成磁界の外部への影響を十分に考慮すればどのような形状でも同様の効果が得られる。
流路７を構成する上基板１１と下基板１２は同一または異種の種類の材質を接合させたものであってもよく、流路形状は実施例のようにチューブ状や同心円状以外の構造であってもよい。
コントローラ６から出力される各信号は実施例のように決まったタイムテーブルで行う必要はなく、独立して各磁界発生部１２を制御し、最適な設定を行うことができる。
なお、本発明の試料混合方法及び装置は、前述の実施例のみに限定するものではなく、例えば流路径の違いや他の分野においても本発明の要旨を逸脱しない範囲の試料混合方法及び装置に適用することができる。
【００１５】
【発明の効果】
以上述べたように、本発明の試料混合方法によれば、異なる種類の試料が粗混合された複合試料を、流路の近傍に磁界を発生する磁界発生部を設け、複合試料の流れ方向に対して垂直方向の磁界を形成し、複合試料を磁気的に混合攪拌するので、試料の流れに対して垂直方向に磁気流を発生でき、試料を二次元的に混合攪拌を行うことができるという効果がある。また、試料に対して物理的な力を加えることが無いため、試料の損傷を抑制することができると共に、試料と非接触に混合攪拌を行うことができるため、接液による不純物の混入を抑えることができるという効果がある。
請求項２に記載の試料混合方法によれば、振動磁界を形成するので、小刻みな振動磁界を加えることにより試料の損傷を抑えることができるとういう効果がある。
請求項３に記載の試料混合方法によれば、パルス的な磁界を形成するので、熱エネルギーの損失を抑えることができ、攪拌効率を向上することができるとともに、磁気流を微動化させることができるため試料の損傷を抑えることができるという効果がある。
請求項４に記載の試料混合方法によれば、流路を挟んで対向配置した磁界発生対により磁界を形成するので、流路内部にかける磁場を容易に大きくすることができ、高い粘度や低い移動度の試料も効率よく混合攪拌を行うことができるという効果がある。
請求項５に記載の試料混合方法によれば、流路の一部を円筒形状の撹拌部とし、試料を撹拌部の中心部から流路の流れ方向と直角方向に流入させて撹拌部の壁面より流出させ、かつ磁界を試料の流れ方向に同心円状に形成し、順次磁界を発生させて回転磁場を形成したので、試料の流れ方向とは別に流路内で円状の流れ（渦流）を形成することができ、攪拌性能を向上することができるという効果がある。また、円中心部から放射状に試料を供給することで全ての試料を確実に混合攪拌することができるという効果がある。
請求項６に記載の試料混合方法によれば、隣接する回転磁場方向が逆方向になるように磁界を発生させるので、回転磁場間で磁気流の摩擦が生じ、試料の衝突頻度を向上することができるという効果がある。
請求項７に記載の試料混合方法によれば、試料が磁場に追従できるのに十分な磁化特性を有する成分を含むようにしたので、磁場形成による磁気力によって直接、試料を混合攪拌することができるという効果がある。また、試料自身が磁化特性を有しなくとも試料中に磁化特性を有する成分が含まれていることで成分の攪拌により目的とする試料を間接的に混合攪拌することが可能となり、攪拌性能を向上することができるという効果がある。
請求項８に記載の試料混合装置によれば、基板からなる流路と、流路近傍に設けられ試料の流れ方向に対して垂直方向に磁界を発生させる磁界発生部と、磁界発生部の磁界を制御するコントローラとを備えたので、試料の流れに対して垂直方向に磁気流を発生でき、試料を二次元的に混合攪拌を行うことができるという効果がある。また、試料に対して物理的な力を加えることが無いため、試料の損傷を抑制することができると共に、試料と非接触に混合攪拌を行うことができ、接液による不純物の混入を抑えることができるという効果がある。
請求項９に記載の試料混合装置によれば、流路を挟んで対向配置した磁界発生対を備えたので、流路内部にかける磁界を容易に大きくすることができ、高い粘度や低い移動度の試料も効率よく混合攪拌できるという効果がある。
請求項１０に記載の試料混合装置によれば、磁界発生対は少なくとも一方の磁界発生部に磁性材料を用いたので、磁界方向を一方の磁界発生部のみで調整でき構造が簡素化できるという効果がある。
請求項１１に記載の試料混合装置によれば、流路の一部を円筒形状とした撹拌部と、撹拌部の中心部に設けた流入口と、撹拌部の壁面に設けた流出口とを備え、磁界発生対を試料の流れ方向に同心円状に配置したので、円中心部から放射状に試料を供給することができるので全ての試料を確実に混合攪拌することができる。また、試料の流れ方向とは別に流路内で回転磁界を形成し、攪拌性能を向上することができるという効果がある。また、円中心部から放射状に試料を供給することで全ての試料を確実に混合攪拌することができると共に、隣接する回転磁場方向が逆方向になるように磁界を発生させることで、回転磁場間で磁気流の摩擦により試料の衝突頻度を向上することができるという効果がある。
請求項１２に記載の試料混合装置によれば、磁界発生部を流路を形成する基板と独立して配置させたので、磁界発生部の異常や流路の目詰り等による不具合時に必要な部分のみを容易に交換でき、保守性能を向上することができるという効果がある。また、磁界発生部と接液する部分が分離できるため、磁界発生部を再利用することができると共に、不純物の混入を抑制することができるという効果がある。
【図面の簡単な説明】
【図１】本発明の第１実施例を示す試料混合装置の断面図
【図２】本発明の第２実施例を示す試料混合装置の断面図
【図３】本発明の第３実施例を示す試料混合装置の横断面図
【図４】本発明の第３実施例を示す試料混合装置の上断面図
【図５】本発明の第４実施例を示す試料混合装置の断面図
【図６】本発明の第５実施例を示す試料混合装置の断面図
【図７】本発明の第６実施例を示す試料混合装置の断面図
【図８】従来の試料混合装置の上断面図
【符号の説明】
１複合試料
２混合試料
３送液ポンプ
４流入口
５流出口
６コントローラ
７流路
１０上基板
１１下基板
１２磁界発生部
１３磁性材料
１４磁界方向
１５磁界発生対
１６磁極上基板
１７磁極下基板
２０回転磁場ａ
２１回転磁場ｂ
２２回転磁場ｃ
５０光圧ミキサ
５１攪拌槽
５２試料ａ
５３試料ｂ[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a sample mixing method and apparatus for mixing and stirring a plurality of molecules, samples, and the like in microchannels used in drug discovery, organic synthesis, chemical analysis, and the like.
[0002]
[Prior art]
In a conventional sample mixing method and apparatus, a stirring unit is provided in a microchannel, and mixing and stirring is directly performed in a liquid by a light pressure mixer disposed in the mixing unit (see, for example, Patent Document 1).
[0003]
[Patent Document 1] Japanese Patent Laid-Open No. 2001-252897 (FIG. 2)
[0004]
FIG. 8 is a cross-sectional view showing a conventional sample mixing apparatus. In the figure, 2 is a mixed sample, 4 is an inlet, 5 is an outlet, 7 is a flow path, 50 is a light pressure mixer, 51 is a stirring tank, 52 is a sample a, and 53 is a sample b. The a52 and the sample b53 are introduced and introduced into the stirring tank 51, and the stirring is performed by irradiating the optical pressure mixer 50 that rotates with the light pressure generated by the light irradiation provided in the stirring tank as a driving force. The two liquids are actively and directly mixed and stirred by rotating in the tank and inducing convection in the sample a and the sample b in the stirring tank.
As described above, in the conventional sample mixing method and apparatus, the light pressure mixer is arranged in the stirring tank, so that the mixing and stirring can be easily performed by light irradiation without having a mechanical drive source. Further, by directly using the convection generated in the stirring tank for mixing and stirring, the mixing efficiency of the mixed sample is drastically increased and the reaction rate is improved.
[0005]
[Problems to be solved by the invention]
However, in the conventional sample mixing method and apparatus, since the light pressure mixer needs to be disposed directly in the flow path, the manufacturing process including the micro flow path becomes complicated, and the processing becomes easier as the flow path width becomes narrower. There was a problem that it became difficult. In addition, since a light source is used as a driving source of the light pressure mixer, a material with poor light transmission cannot be used as a substrate, and a sample that can be mixed and stirred may cause a decrease in mixing efficiency due to light transmittance. was there. Furthermore, since mixing and stirring is performed by mechanically generating convection, there is a problem that the sample may be damaged when the optical pressure mixer rotates.
Therefore, the present invention has been made in view of such problems, and a sample mixing method and apparatus capable of efficiently mixing and stirring a plurality of samples without taking a means for mixing and stirring directly in a flow path. The purpose is to provide.
[0006]
[Means for Solving the Problems]
In order to solve the above problems, the present invention is configured as follows.
The invention according to claim 1 is a sample mixing method in which a composite sample in which different types of samples are roughly mixed is mixed and stirred in a flow path, and a magnetic field generator that generates a magnetic field is provided in the vicinity of the flow path. The magnetic field generator forms a magnetic field perpendicular to the flow direction of the composite sample, and magnetically mixes and stirs the composite sample.
Thus, a magnetic flow can be generated in a direction perpendicular to the flow direction of the sample, and the sample can be mixed and stirred two-dimensionally. In addition, since no physical force is applied to the sample, damage to the sample can be suppressed, and mixing and agitation can be performed in a non-contact manner with the sample, and contamination of impurities due to liquid contact can be suppressed. Can do.
According to a second aspect of the present invention, the magnetic field is an oscillating magnetic field whose intensity changes periodically.
As a result, the magnetic flow formed in the flow path by the magnetic field can be generated alternately in the direction perpendicular to the flow direction of the sample, and continuous mixing and stirring performance can be improved. it can. Moreover, damage to the sample can be suppressed by generating an oscillating magnetic field every minute.
According to a third aspect of the present invention, the magnetic field is an oscillating magnetic field whose intensity changes periodically.
Since it has become like this, the loss of thermal energy can be suppressed and the stirring efficiency can be improved. In addition, the magnetic flow can be finely controlled, and damage to the sample can be suppressed.
According to a fourth aspect of the present invention, the magnetic field is formed by a magnetic field generating pair arranged opposite to each other with the flow path interposed therebetween.
Thus, the magnetic field applied to the inside of the flow path can be easily increased, and a sample with high viscosity and low mobility can be mixed and stirred efficiently.
According to a fifth aspect of the present invention, a part of the flow path is a cylindrical stirring section, and the sample is allowed to flow from the central portion of the stirring section in a direction perpendicular to the flow direction of the flow path. The rotating magnetic field is formed by causing the magnetic field to flow out of the wall surface, forming the magnetic field concentrically in the flow direction of the sample, and sequentially generating the magnetic field.
Thus, a circular flow (vortex flow) can be formed in the flow path separately from the sample flow direction, and the stirring performance can be improved. Moreover, all samples can be reliably mixed and stirred by supplying the samples radially from the center of the circle.
According to a sixth aspect of the present invention, the direction of the magnetic field of the rotating magnetic field is alternately changed in the radial direction.
Thus, friction of the magnetic flow is generated between the rotating magnetic fields, and the collision frequency of the sample can be improved.
According to a seventh aspect of the present invention, the sample includes a component having magnetization characteristics.
Thus, the sample can be directly mixed and stirred by the magnetic force generated by the magnetic field formation. In addition, even if the sample itself does not have magnetizing characteristics, the sample contains a component having magnetizing characteristics, which makes it possible to indirectly mix and stir the target sample by stirring the components. Can be improved.
According to an eighth aspect of the present invention, there is provided a flow path formed of a substrate, a magnetic field generation unit that is provided near the flow path and generates a magnetic field in a direction perpendicular to the flow direction of the sample, and a magnetic field of the magnetic field generation unit. And a controller for controlling.
Thus, a magnetic flow can be generated in a direction perpendicular to the flow direction of the sample, and the sample can be mixed and stirred two-dimensionally. In addition, since no physical force is applied to the sample, damage to the sample can be suppressed, and mixing and agitation can be performed in a non-contact manner with the sample, and contamination of impurities due to liquid contact can be suppressed. Can do.
According to a ninth aspect of the present invention, the magnetic field generation unit is a magnetic field generation pair arranged to face each other with the flow path interposed therebetween.
Thus, the magnetic field applied to the inside of the flow path can be easily increased, and a sample with high viscosity and low mobility can be mixed and stirred efficiently.
According to a tenth aspect of the present invention, the magnetic field generation pair includes a magnetic material provided on at least one of the magnetic field generation units.
Thus, the direction of the magnetic field can be adjusted by only one magnetic field generation unit, and the structure can be simplified.
The invention according to claim 11 includes a mixing portion in which a part of the flow path is cylindrical, an inlet provided in a central portion of the mixing portion, and an outlet provided on a wall surface of the stirring portion. The magnetic field generating pairs are arranged concentrically in the flow direction of the sample.
As a result, magnetic fields are sequentially generated according to the arrangement order of the magnetic field generators, and a circular flow (rotating magnetic field) can be formed in the flow path separately from the flow direction of the sample. Can be improved. In addition, by supplying the sample radially from the center of the circle, all the samples can be mixed and stirred reliably, and by generating a magnetic field so that the adjacent rotating magnetic field direction is opposite, Thus, the collision frequency of the sample can be improved by friction of the magnetic flow.
According to a twelfth aspect of the present invention, the magnetic field generator is arranged independently of a substrate forming the flow path.
Thus, only necessary portions can be easily replaced in the event of a malfunction due to an abnormality in the magnetic field generation unit or clogging of the flow path, and maintenance performance can be improved. In addition, the portion in contact with the magnetic field generation unit can be separated, the magnetic field generation unit can be reused, and contamination of impurities can be suppressed.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
Hereinafter, specific embodiments of the present invention will be described with reference to the drawings.
[0008]
(First embodiment)
FIG. 1 is a sectional view of a sample mixing apparatus showing a first embodiment of the present invention. In the figure, the same reference numerals are used for common parts, 1 is a composite sample, 2 is a mixed sample, 3 is a liquid feeding device, 4 is an inlet, 5 is an outlet, 6 is a controller, 7 is a flow path, Reference numeral 10 denotes an upper substrate, 11 denotes a lower substrate, 12 denotes a magnetic field generator, and 14 denotes a magnetic field direction.
As the composite sample 1, a fluorescent dye and a DNA fragment extracted from yeast were used and introduced into the inflow port 4 of the microchannel from a syringe-driven liquid feeding device 3. The channel 7 has a cross section of 500 μm × 200 μm and a length of 50 mm, and the magnetic field generator 12 is a micromachined electromagnet.
Next, the operation of this embodiment will be described.
The composite sample 1 is introduced at a specified flow rate from the inlet 4 of the micro-processed flow path 7 using the liquid feeding device 3. Next, when a signal is input from the controller 6 to the magnetic field generator 12 arranged on the upper substrate 10, a magnetic flux is generated between the upper substrate 10 and the lower substrate 11 through the flow path 7. Since the magnetic flux is formed in a direction perpendicular to the flow direction of the composite sample 1, the composite sample 1 receives a force when the magnetic field is generated by the magnetic flux in the composite sample 1, and a magnetic flow is generated. The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. Next, when a magnetic flux in the opposite direction is generated, the composite sample 1 is again mixed and stirred by the magnetic flow in the opposite direction to the previous one. As shown in the magnetic field direction 14, the mixed sample 2 can be efficiently collected by continuously performing the reciprocating motion of the magnetic field.
For example, when the composite sample 1 supplied at a total of 10 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0009]
(Second embodiment)
FIG. 2 is a cross-sectional view of a sample mixing apparatus showing a second embodiment of the present invention. In the figure, 15 is a magnetic field generation pair.
A composite sample 1 and a flow path 7 similar to those of the first example were used, and a micro-machined electromagnet was used for the magnetic field generator 12.
Next, the operation of this embodiment will be described.
The composite sample 1 is introduced at a specified flow rate from the inlet 4 of the micro-processed flow path 7 using the liquid feeding device 3. Next, when a signal is input from the controller 6 to the magnetic field generator 12 arranged on the upper substrate 10 and the lower substrate 11, a magnetic flux is generated between the upper substrate 10 and the lower substrate 11 through the flow path 7. For example, when the magnetic field direction 14 is downward, the magnetic field generation unit 12 disposed on the upper substrate 10 is directed in the flow path 7 and the magnetic field generation unit 12 disposed on the lower substrate 11 is moved from the flow path 7 to the lower substrate 11. Magnetic flux is formed in each direction toward the outside. Since the magnetic flux is formed in a direction perpendicular to the flow direction of the composite sample 1, the composite sample 1 receives a force when the magnetic field is generated by the magnetic flux in the composite sample 1, and a magnetic flow is generated. The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. When the magnetic field direction 14 is upward, the composite sample 1 generates a magnetic flow in a direction opposite to the previous direction by reversing the magnetic flux applied to each substrate, and mixing and stirring are performed again. As shown in the magnetic field direction 14, the mixed sample 2 can be efficiently collected by continuously reciprocating the magnetic field between the magnetic field generation pairs 15. Basically, by synchronizing the signal applied from the controller 6 to the magnetic field generating pair 15 between the upper substrate 10 and the lower substrate 11, a higher combined magnetic flux than the magnetic flux of the single magnetic field generating unit 12 can be obtained, which is efficient. Mixing and stirring can be promoted.
For example, when the composite sample 1 supplied at a total of 10 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0010]
(Third embodiment)
FIG. 3 is a transverse sectional view of a sample mixing apparatus showing a third embodiment of the present invention, and FIG. 4 is an upper sectional view of FIG. In the figure, 20 is a rotating magnetic field a, 21 is a rotating magnetic field b, and 22 is a rotating magnetic field c.
A composite sample 1 similar to that in the first example was used, and the flow path 7 having a diameter of 40 mm and a height of 200 μm was used, and the magnetic field generator 12 was a micromachined electromagnet.
Next, the operation of this embodiment will be described.
When the inflow port 4 is provided at the center of the circle of the flow path 7 that has been micro-processed into a disk shape, and the composite sample 1 is introduced into the flow path 7 at a predetermined flow rate by the liquid delivery device 3, the composite sample 1 is radiated from the inflow port 4. In the flow path 7 almost evenly. Here, a magnetic flux is generated between the upper substrate 10 and the lower substrate 11 through the flow path 7 by inputting a signal from the controller 6 to the magnetic field generator 12 disposed on the upper substrate 10. Since the magnetic field is formed in a direction perpendicular to the flow direction of the composite sample 1, the magnetic field is generated by the magnetic flux in the composite sample 1 and the composite sample 1 receives a force to generate a magnetic flow. The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. Next, by mixing the magnetic flux applied to the upper substrate 10 in the reverse direction, the composite sample 1 is mixed and stirred again by the generation of a magnetic flow in the reverse direction.
Moreover, the composite sample 1 can be moved by forming a rotating magnetic field by configuring the magnetic field generator 12 concentrically as shown in FIG. 4 and making the magnetic flow spiral. For example, when the rotating magnetic field a20 is formed clockwise with a, b, c... H, a, a sinusoidal magnetic flow can be obtained in the flow path 7, and the composite sample 1 is rotated clockwise. Receive power. Therefore, the composite sample 1 receives a radial force, a force perpendicular to the flow direction, and a clockwise force, so that three-dimensional mixing and stirring is performed and the mixing rate is greatly increased. Can do. A large eddy current can be obtained by rotating clockwise including the rotating magnetic field b21 and the rotating magnetic field c22. Further, when the rotating magnetic field a20 is rotated clockwise, the rotating magnetic field b21 is counterclockwise, and the rotating magnetic field c22 is formed clockwise, a large friction is generated at the boundary between the rotating magnetic fields, and a higher mixing ratio can be obtained. The mixed sample 2 is sequentially discharged from a plurality of outlets 5 provided.
For example, when the composite sample 1 supplied at a total of 20 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0011]
(Fourth embodiment)
FIG. 5 is a sectional view of a sample mixing apparatus showing a fourth embodiment of the present invention. In the figure, 13 is a magnetic material.
A composite sample 1 similar to that in the first example was used, a flow path 7 similar to that in the third example was used, and a micro-machined electromagnet was used as the magnetic field generator 12.
Next, the operation of this embodiment will be described.
When the inflow port 4 is provided at the center of the circle of the flow path 7 that has been micro-processed into a disk shape, and the composite sample 1 is introduced into the flow path 7 at a predetermined flow rate by the liquid delivery device 3, the composite sample 1 is radiated from the inflow port 4. In the flow path 7 almost evenly. Here, a magnetic flux is generated between the upper substrate 10 and the lower substrate 11 through the flow path 7 by inputting a signal from the controller 6 to the magnetic field generator 12 disposed on the upper substrate 10. At this time, the magnetic material 13 constituting the magnetic field generating pair 15 is arranged on the lower substrate 11, and the magnetic field direction 14 in the flow path 7 is changed according to the strength of the magnetic field generating unit 12 arranged on the upper substrate 10. Let Since the magnetic field direction 14 is formed in a direction perpendicular to the flow direction of the composite sample 1, the magnetic field due to the magnetic flux is formed in the composite sample 1, and the composite sample 1 receives a force to generate a magnetic flow, The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. Next, by mixing the magnetic flux applied to the upper substrate 10 in the reverse direction, the composite sample 1 is mixed and stirred again by the generation of a magnetic flow in the reverse direction. By using the magnetic material 13 instead of the magnetic field generator 12, the apparatus can be simplified and miniaturized, and the controller 6 does not require complicated elements.
For example, when the composite sample 1 supplied at a total of 20 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0012]
(5th Example)
FIG. 6 is a sectional view of a sample mixing apparatus showing a fifth embodiment of the present invention.
A composite sample 1 similar to that in the first example was used, a flow path 7 similar to that in the third example was used, and a micro-machined electromagnet was used as the magnetic field generator 12.
Next, the operation of this embodiment will be described.
When the inflow port 4 is provided at the center of the circle of the flow path 7 that has been micro-processed into a disk shape, and the composite sample 1 is introduced into the flow path 7 at a predetermined flow rate by the liquid delivery device 3, the composite sample 1 is radiated from the inflow port 4. In the flow path 7 almost evenly. Here, a magnetic flux is generated between the upper substrate 10 and the lower substrate 11 through the flow path 7 by inputting a signal from the controller 6 to the magnetic field generator 12 disposed on the substrate 11 as the upper substrate 10. Since the magnetic field direction 14 is formed in a direction perpendicular to the flow direction of the composite sample 1, the magnetic field due to the magnetic flux is formed in the composite sample 1, and the composite sample 1 receives a force to generate a magnetic flow, The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. Next, by mixing the magnetic field applied to the upper substrate 10 in the opposite direction, the composite sample 1 is again mixed and stirred by the magnetic flow in the opposite direction to the previous one.
The upper substrate 10 and the lower substrate 11 are each provided with a magnetic field generator 12 that forms a magnetic field generation pair 15, and the magnetic field direction 14 in the flow path 7 is changed according to the combined magnetic field in each magnetic field generation pair 15. Similarly to the third embodiment, the magnetic field generator 12 is concentrically formed to form a rotating magnetic field, and the composite sample 1 can be moved by a spiral magnetic flow. Therefore, the composite sample 1 has a radial force. As a result, a force in a direction perpendicular to the flow direction and a clockwise force are received, and three-dimensional mixing and stirring is performed, so that the mixing rate can be significantly increased. Further, by configuring adjacent rotating magnetic fields in opposite directions, a large friction is generated at the boundary between the rotating magnetic fields, and a higher mixing ratio can be obtained. Basically, by synchronizing the signal applied from the controller 6 to the electrode pair 15 between the upper substrate 10 and the lower substrate 11, it is possible to obtain a higher combined magnetic flux than the magnetic flux of the single magnetic field generator 12, which is efficient. Mixing and stirring can be promoted.
For example, when the composite sample 1 supplied at a total of 20 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0013]
(Sixth embodiment)
FIG. 7 is a sectional view of a sample mixing apparatus showing a sixth embodiment of the present invention. In the figure, 16 is a magnetic pole upper substrate, and 17 is a magnetic pole lower substrate.
A composite sample 1 similar to that in the first example was used, a flow path 7 similar to that in the third example was used, and a micro-machined electromagnet was used as the magnetic field generator 12.
Next, the operation of this embodiment will be described.
When the inflow port 4 is provided at the center of the circle of the flow path 7 that has been micro-processed into a disk shape, and the composite sample 1 is introduced into the flow path 7 at a predetermined flow rate by the liquid delivery device 3, the composite sample 1 is radiated from the inflow port 4. In the flow path 7 almost evenly. The upper magnetic pole substrate 16 and the lower magnetic pole substrate 17 on which the magnetic field generating unit 12 is disposed are respectively disposed on the upper substrate 10 and the lower substrate 11, and a signal is input from the controller 6 to the magnetic field generating unit 12 through the flow path 7. Magnetic flux is generated between the substrate 10 and the lower substrate 11. Since the magnetic field direction 14 is formed in a direction perpendicular to the flow direction of the composite sample 1, the magnetic field due to the magnetic flux is formed in the composite sample 1, and the composite sample 1 receives a force to generate a magnetic flow, The composite sample 1 causes a collision reaction due to the mean free process by the magnetic flow, and is mixed and stirred in the flow path 7. Next, by mixing the magnetic flux applied to the upper substrate 10 in the reverse direction, the composite sample 1 is again mixed and stirred by the magnetic flow in the reverse direction.
The magnetic field direction 14 in the flow path 7 is changed in accordance with the combined magnetic field in each magnetic field generation pair 15, and the magnetic field generation unit 12 is configured concentrically as in the third embodiment to form a rotating magnetic field. Since the composite sample 1 is subjected to a radial force, a force perpendicular to the flow direction, and a clockwise force, three-dimensional mixing and stirring is performed. The mixing rate can be greatly increased. Further, by configuring adjacent rotating magnetic fields in opposite directions, a large friction is generated at the boundary between the rotating magnetic fields, and a higher mixing ratio can be obtained. Basically, by synchronizing the signal applied from the controller 6 to the electrode pair 15 between the upper substrate 10 and the lower substrate 11, it is possible to obtain a higher combined magnetic flux than the magnetic flux of the single magnetic field generator 12, which is efficient. Mixing and stirring can be promoted. Since the magnetic field generator 12 is not embedded in each substrate, only necessary parts can be easily replaced in the event of a malfunction due to an abnormality in the magnetic field generator or clogging of the flow path, and the maintenance performance can be improved. In addition, since the portion in contact with the magnetic field generation unit 12 can be separated, contamination of impurities can be suppressed. By making the magnetic field generator 12 itself a linear structure, finer processing can be performed.
For example, when the composite sample 1 supplied at a total of 20 μL / min was mixed and stirred, the mixed sample 2 was collected, and when the mixing rate was measured by the emission intensity with a fluorescence analyzer, the improvement of the mixing rate could be confirmed.
[0014]
In this example, a fluorescent dye and a DNA fragment extracted from yeast were used as the composite sample 1. However, by using a sample in which a component having magnetization characteristics was previously bonded to the end of the sample itself, a magnetic field due to magnetic flux formation was used. Can directly mix and stir the sample. In addition, even if the sample itself does not have magnetizing properties, the buffer solution contains a component having magnetizing properties, which makes it possible to indirectly mix and stir the target sample by stirring the components. The performance can be improved.
Although a pump is used as the transport device 3 for each sample, the same effect can be obtained by using an electrophoretic transport means. The magnetic field generator 12 is not limited to the shape shown in the embodiment, and the same effect can be obtained in any shape as long as the influence of the combined magnetic field on each magnetic field generation pair is sufficiently considered.
The upper substrate 11 and the lower substrate 12 constituting the flow path 7 may be formed by joining the same or different kinds of materials, and the flow path shape is a structure other than a tube shape or a concentric shape as in the embodiment. There may be.
Each signal output from the controller 6 does not need to be performed according to a fixed time table as in the embodiment, and each magnetic field generator 12 can be independently controlled to perform optimum setting.
Note that the sample mixing method and apparatus of the present invention are not limited to the above-described embodiments. For example, the sample mixing method and apparatus are within a range that does not depart from the gist of the present invention even in a difference in flow path diameter and other fields. Can be applied.
[0015]
【The invention's effect】
As described above, according to the sample mixing method of the present invention, a composite sample in which different types of samples are roughly mixed is provided with a magnetic field generation unit that generates a magnetic field in the vicinity of the flow path, so that the composite sample flows in the flow direction. On the other hand, since a magnetic field in the vertical direction is formed and the composite sample is magnetically mixed and stirred, a magnetic flow can be generated in a direction perpendicular to the flow of the sample, and the sample can be mixed and stirred in two dimensions. effective. In addition, since no physical force is applied to the sample, damage to the sample can be suppressed, and mixing and agitation can be performed in a non-contact manner with the sample, so that mixing of impurities due to liquid contact is suppressed. There is an effect that can be.
According to the sample mixing method of the second aspect, since the oscillating magnetic field is formed, there is an effect that damage to the sample can be suppressed by applying the oscillating magnetic field every minute.
According to the sample mixing method of claim 3, since a pulsed magnetic field is formed, loss of heat energy can be suppressed, stirring efficiency can be improved, and magnetic flow can be finely adjusted. Therefore, there is an effect that damage to the sample can be suppressed.
According to the sample mixing method of the fourth aspect, since the magnetic field is formed by the magnetic field generating pairs arranged opposite to each other with the flow channel interposed therebetween, the magnetic field applied to the inside of the flow channel can be easily increased, and high viscosity or low The mobility sample can also be efficiently mixed and stirred.
According to the sample mixing method of claim 5, a part of the flow path is a cylindrical stirring part, and the sample is allowed to flow from the center part of the stirring part in a direction perpendicular to the flow direction of the flow path to Since the magnetic field is formed concentrically in the flow direction of the sample and the magnetic field is sequentially generated to form the rotating magnetic field, a circular flow (vortex) is generated in the flow path separately from the flow direction of the sample. It can be formed, and the stirring performance can be improved. Moreover, there is an effect that all the samples can be reliably mixed and stirred by supplying the samples radially from the center of the circle.
According to the sample mixing method of the sixth aspect, the magnetic field is generated so that the adjacent rotating magnetic field directions are opposite to each other, so that magnetic flow friction occurs between the rotating magnetic fields, and the collision frequency of the sample is improved. There is an effect that can be.
According to the sample mixing method of the seventh aspect, since the sample includes a component having a magnetization characteristic sufficient to follow the magnetic field, the sample can be directly mixed and stirred by the magnetic force generated by the magnetic field formation. There is an effect that can be done. In addition, even if the sample itself does not have magnetizing characteristics, the sample contains a component having magnetizing characteristics, which makes it possible to indirectly mix and stir the target sample by stirring the components. There is an effect that it can be improved.
According to the sample mixing apparatus of claim 8, the flow path formed of the substrate, the magnetic field generation unit that is provided in the vicinity of the flow path and generates a magnetic field in the direction perpendicular to the flow direction of the sample, and the magnetic field of the magnetic field generation unit Therefore, there is an effect that a magnetic flow can be generated in a direction perpendicular to the flow of the sample, and the sample can be mixed and stirred two-dimensionally. In addition, since no physical force is applied to the sample, damage to the sample can be suppressed, and mixing and agitation can be performed in a non-contact manner with the sample, and contamination of impurities due to liquid contact can be suppressed. There is an effect that can be.
According to the sample mixing device of the ninth aspect, since the magnetic field generating pair arranged opposite to each other with the flow channel interposed therebetween, the magnetic field applied to the inside of the flow channel can be easily increased, and high viscosity and low mobility can be obtained. This sample also has the effect of being able to mix and stir efficiently.
According to the sample mixing apparatus of claim 10, since the magnetic field generating pair uses a magnetic material for at least one of the magnetic field generating portions, the magnetic field direction can be adjusted only by one of the magnetic field generating portions, and the structure can be simplified. There is.
According to the sample mixing device of claim 11, the stirring unit having a cylindrical part of the flow path, the inlet provided in the center of the stirring unit, and the outlet provided in the wall surface of the stirring unit. In addition, since the magnetic field generating pairs are arranged concentrically in the sample flow direction, the sample can be supplied radially from the center of the circle, so that all the samples can be mixed and stirred reliably. Further, there is an effect that a rotating magnetic field can be formed in the flow path separately from the flow direction of the sample, and the stirring performance can be improved. In addition, by supplying the sample radially from the center of the circle, all the samples can be mixed and stirred reliably, and by generating a magnetic field so that the adjacent rotating magnetic field direction is opposite, Thus, there is an effect that the collision frequency of the sample can be improved by friction of the magnetic flow.
According to the sample mixing apparatus of claim 12, since the magnetic field generation unit is arranged independently of the substrate that forms the flow path, the part necessary for malfunctions due to abnormalities in the magnetic field generation unit, clogging of the flow path, etc. Only can be easily replaced, and the maintenance performance can be improved. In addition, since the portion in contact with the magnetic field generation unit can be separated, the magnetic field generation unit can be reused, and impurities can be prevented from being mixed.
[Brief description of the drawings]
FIG. 1 is a cross-sectional view of a sample mixing apparatus showing a first embodiment of the present invention.
FIG. 2 is a sectional view of a sample mixing apparatus showing a second embodiment of the present invention.
FIG. 3 is a cross-sectional view of a sample mixing apparatus showing a third embodiment of the present invention.
FIG. 4 is a top sectional view of a sample mixing apparatus showing a third embodiment of the present invention.
FIG. 5 is a sectional view of a sample mixing apparatus showing a fourth embodiment of the present invention.
FIG. 6 is a sectional view of a sample mixing apparatus showing a fifth embodiment of the present invention.
FIG. 7 is a sectional view of a sample mixing apparatus showing a sixth embodiment of the present invention.
FIG. 8 is a top sectional view of a conventional sample mixing apparatus
[Explanation of symbols]
1 Composite sample
2 Mixed samples
3 Liquid feed pump
4 Inlet
5 outlet
6 Controller
7 Channel
10 Upper substrate
11 Lower substrate
12 Magnetic field generator
13 Magnetic materials
14 Magnetic field direction
15 Magnetic field generation pair
16 Pole substrate
17 Under magnetic pole substrate
20 Rotating magnetic field a
21 Rotating magnetic field b
22 Rotating magnetic field c
50 Light pressure mixer
51 Mixing tank
52 Sample a
53 Sample b

Claims

In a sample mixing method of mixing and stirring a composite sample in which different types of samples are roughly mixed in a flow path,
A magnetic field generator for generating a magnetic field is provided in the vicinity of the flow path, and a magnetic field perpendicular to the flow direction of the composite sample is formed by the magnetic field generator, and the composite sample is magnetically mixed and stirred. A sample mixing method.

The sample mixing method according to claim 1, wherein the magnetic field is an oscillating magnetic field whose intensity changes periodically.

The sample mixing method according to claim 1, wherein the magnetic field is a pulsed magnetic field.

The sample mixing method according to any one of claims 1 to 3, wherein the magnetic field is formed by a magnetic field generating pair arranged to face each other with the flow channel interposed therebetween.

A part of the flow path is a cylindrical stirring section, the sample is allowed to flow from the central portion of the stirring section in a direction perpendicular to the flow direction of the flow path and flow out of the wall surface of the stirring section, and the magnetic field is 5. The sample mixing method according to claim 1, wherein the sample is formed concentrically in a flow direction of the sample, and a rotating magnetic field is formed by sequentially generating a magnetic field.

6. The sample mixing method according to claim 5, wherein the rotating magnetic field is configured such that the direction of the magnetic field alternately changes in the radial direction.

The sample mixing method according to claim 1, wherein the sample includes a component having magnetization characteristics.

A flow path comprising a substrate, a magnetic field generator provided in the vicinity of the flow path for generating a magnetic field in a direction perpendicular to the flow direction of the sample, and a controller for controlling the magnetic field of the magnetic field generator. A sample mixing apparatus.

9. The sample mixing apparatus according to claim 8, wherein the magnetic field generation unit is a magnetic field generation pair arranged to face each other with the flow channel interposed therebetween.

The sample mixing apparatus according to claim 8 or 9, wherein the magnetic field generating pair is provided with a magnetic material in at least one of the magnetic field generating portions.

A stirring portion having a cylindrical shape in a part of the flow path; an inlet provided in a central portion of the stirring portion; and an outlet provided in a wall surface of the stirring portion; The sample mixing apparatus according to any one of claims 8 to 10, wherein the sample mixing apparatus is arranged concentrically in a flow direction.

The sample mixing apparatus according to any one of claims 8 to 11, wherein the magnetic field generation unit is arranged independently of a substrate forming the flow path.